Quantitative analysis of intraneuronal transport in human iPS neurons
Quantitative analysis of intraneuronal transport in human iPS neurons
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人类 iPS 神经元神经元内转运的定量分析
DOI：
10.1016/j.jphs.2015.06.006
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Goshima Y
中科院分区：
文献类型：
--
作者：
Nakamura H;Yamashita N;Kanamaru Y;Tachibana T;Sekino Y;Chen S;Gotoh T;Tanaka F;Goshima Y
诱导多能干细胞(IPS)是研究疾病机制和开发新药的重要工具。神经元内转运是神经元生存和功能的基础，易受各种药物和化学物质的影响，在某些神经退行性疾病中会受到干扰。我们应用了一种量化轴突运输的方法，通过对沿轴突移动的CM-DiI标记颗粒进行计数，这使得我们第一次能够监测和定量从iPS细胞(iCell神经元)分化出的人类神经元的神经元内运输。我们评估了几种抗肿瘤药物的急性效应，这些药物先前已被证明会影响神经元内转运。长春新碱、紫杉醇和奥沙利铂可减少轴突移动颗粒的数量。然而，顺铂对神经元内转运没有影响，这与我们之前的报告相反，该报告表明顺铂抑制了鸡背根神经节神经元的转运。我们的系统可能是一种有用的方法来评估人iPS神经元的神经元内运输和神经毒性。
Induced pluripotent stem (iPS) cells are promising tools to investigate disease mechanism and develop new drugs. Intraneuronal transport, which is fundamental for neuronal survival and function, is vulnerable to various pharmacological and chemical agents and is disrupted in some neurodegenerative disorders. We applied a quantification method for axonal transport by counting CM-DiI–labeled particles traveling along the neurite, which allowed us to monitor and quantitate, for the first time, intraneuronal transport in human neurons differentiated from iPS cells (iCell neurons). We evaluated the acute effects of several anti-neoplastic agents that have been previously shown to affect intraneuronal transport. Vincristine, paclitaxel and oxaliplatin decreased the number of moving particle along neurites. Cisplatin, however, produced no effect on intraneuronal transport, which is in contrast to our previous report indicating that it inhibits transport in chick dorsal root ganglion neurons. Our system may be a useful method for assessing intraneuronal transport and neurotoxicity in human iPS neurons.